1887

Abstract

Lipo-oligosaccharide (LOS) is a major surface component and virulence factor of the human respiratory pathogen . Two late acyltransferase genes, and , have been identified involved in the incorporation of acyloxyacyl-linked secondary acyl chains into lipid A during LOS biosynthesis. In this study, a double mutant with a deletion of both the and genes in strain O35E was constructed and named O35ElpxXL. Structural analysis of lipid A showed that the O35ElpxXL mutant lacked two decanoic acids (10 : 0) and one dodecanoic (lauric) acid (12 : 0). In comparison with the O35E parental strain and the single mutants O35ElpxX and O35ElpxL, the double mutant O35ElpxXL displayed prominently decreased endotoxin content, reduced resistance to normal human serum and accelerated bacterial clearance at 0, 3 and 6 h after an aerosol challenge in a mouse model of bacterial pulmonary clearance. These results indicate that these two genes encoding late acyltransferases responsible for lipid A biosynthesis jointly contribute to the biological activities and pathogenicity of The double mutant O35ElpxXL with dramatically reduced toxicity is proposed as a potential vaccine candidate against infections for further investigation.

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2013-06-01
2019-10-18
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